| Objective To evaluate the efficacy and safety of mycophenolate mofetil taken orally for 24 weeks plus methyprednisolone intravenous infusion for 12 weeks in patients with active moderate to severe thyroid associated ophthalmopathy(TAO)in order to obtain a more effective modality.Methods Infirmation of patients who were diagnosed with active moderate-to-severe thyroid associated ophthalmopathy in the Second Hospital of Dalian Medical University from September 2019 to April 2022 were collected.Patients who were treated with methylprednisolone intravenous infusion and combined with methylprednisolone intravenous infusion plus mycophenolate mofetil oral administration were included in this study.Inclusion criteria: Patients aged elder than or equal to 18 years old,and diagnosed as active moderate to severe thyroid associated ophthalmopathy were eligible to participate if they had euthyroidism for at least 6 weeks with antithyroid drugs,and had normal heart,liver and kidney functions.The patients were divided into combination group and monotherapy group according to the treatment regime.All patients were treated with methylprednisolone intravenous infusion for 12 weeks,0.5 g once a week in the first 6 weeks and 0.25 g once a week in the last 6 weeks.In addition,mycophenolate mofetil was taken orally in the combination group 1.00g/day.In this study,subjective and objective methods both were used to evaluate the clinical efficacy in order to make a more comprehensive assessment.The quality of life questionaire for thyroid associated ophthalmopothy(TAO-Qol)is the first choice for subjective patients’ self-assessment(PRO).The objective clinician’s assessment(CRO)was evaluated by comprehensive indexes including CAS score(excluding spontaneous retrobulbar pain and pain on attempted upward or downward gaze),exophthalmos,eyelid apperture and eye movement,reoponse defined as a reduction of at least two measures of above index without simultaneous deterioration of any of the ophthalmic parameters of the index.The overall response rate and the scores of quality of life questionaire for thyroid associated ophthalmopothy(TAO-Qol),soft tissue involvement,visual acuity,diplopia and CAS(seven-point scale)were compared between the two groups at 12 and 24 weeks,adverse events were recorded either.Statistics mainly used independent sample t-test or two independent sample wilcoxon signed rank test,chi-square test or mcnemar test and so on.For the overall response of the two groups,the efficacy was reported with an odds ratio(OR)of 95% CIS,adverse events were recorded either.Results1.Clinician reported outcome:At the 12 th week of clinician reported evaluation,5 out of 16 patients(41.3%)in the monotherapy group and 10 of 21 patients(47.6%)in the combination group were effective to the treatment(OR 2.00,95% CI 0.51-7.80,P=0.50).At 24 weeks,the overall response rate increased to 61.9% in the combination group and slightly to 50.0% in the monotherapy group(OR 1.625,95%CI 0.43-6.07,P=0.52).At 12 weeks,the score of CAS in the combination group decreased from 4(3,4)to 2(1,3),the score of CAS in the monotherapy group decreased from 4(3,5)to 2(2,3)(P=0.208),and at 24 weeks decreased to 1(1,1.5)and 2(1,2.75),respectively(P=0.009).The score of CAS,soft tissue involvement,diplopia,visual acuity,proptosis,eyelid apperture and eye movement were significantly improved in the combination group at the 24 th week compared with the monotherapy group,but there was no statistical difference in the change of visual acuity,eyelid apperture and decrease of eye movement.2.Patient reported outcome: At the 12 th week,the scores of TAO-Qol in the combination group increased significantly from 69.79 ± 9.65 at baseline to 81.25 ±9.53(P < 0.001),while those in the monotherapy group increased from 68.75 ± 9.75 at first to 71.68 ± 7.86(P=0.004),with statistical significance between the two groups(P=0.003).At the 24 th week,the score of TAO-Qol in the combination group was further improved to 83.48 ± 9.12(P < 0.001),while that in the monotherapy group was 72.66 ± 9.92(P=0.055),which was statistically significant between the two groups(P=0.001).3.Adverse events occurred in 2 of 21 patients treated with MMF(9.52%)and in7 of 16 patients treated with GC(43.75%).The difference between the two groups was statistically significant(P=0.024).Conclusion In patients with active and moderate-to-severe thyroid associated ophthalmopathy,adding moderate dose of mycophenolate mofetil on the basis of moderate dose of methylprednisolone intravenous infusion can effectively improve the overall response rate at 12 weeks and 24 weeks.After 12 weeks of methyprednisolone,the ophthalmic symptoms and signs of patients were continuously improved,and the improvement of proptosis and diplopia showed advantages that previous monotherapy group did not acheive,also could improve the quality of life of patients effectively.Mycophenolate mofetil combined with methylprednisolone is more effective and safer than monotherapy in the treatment of active moderate-to-severe thyroid associated ophthalmopathy,and has considerable economic applicability. |
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